Abstract
During the half century following its discovery, the l-glutamate-producing microorganism Corynebacterium glutamicum has played a leading role in the amino acid fermentation industry. Due to its importance as an amino acid producer, C. glutamicum is also one of the best-investigated microorganisms, evidenced by the extensive body of relevant literature and patents. In the past quarter century, various genetic engineering tools and global analysis techniques for this bacterium have been developed and successfully applied, giving a thorough understanding of its physiology and permitting the development of efficient production strains. The advances enhancing the usefulness of this bacterium for amino acid production over the last decade can be summarized in five points: (1) Metabolic engineering strategies are expanding from the core biosynthetic pathways to include central metabolism, cofactor-regeneration systems, uptake and export systems, energy metabolism, global regulation, and stress responses; strain improvement is bound to thereby optimize entire cellular systems. (2) Systems biology for this bacterium is almost capable of predicting targets to be engineered and metabolic states that will yield maximum production; these developments should allow rational metabolic design. (3) Rapid strides in genome analysis have revolutionized strain improvement methodology, allowing reengineering of more efficient producers through knowledge of the mutations that have accumulated over years of industrial strain development. (4) The spectra of both products and assimilable carbon sources of this bacterium have expanded, leading to the development of, e.g., production strains of serine and methionine that could not be produced effectively from glucose and strains that can utilize alternative feedstocks that do not compete with human food or energy sources. (5) Recent identification of a putative mechanosensitive channel as a possible glutamate exporter has provided valuable insight into the glutamate production mechanism which had long been the central question concerning the industrial biotechnology of C. glutamicum. This chapter describes advances in the production of amino acids by C. glutamicum, with special focus on the technology and strategies for molecular strain improvement.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Ajinomoto (2007) Fact sheets: amino acids business and feed-use amino acids business. http://www.ajinomoto.com/ar/i_r/pdf/fact/Aminoacids-Oct2007.pdf http://www.ajinomoto.com/ar/i_r/pdf/fact/Feed-useAA-Oct2007.pdf
Appleton J (2002) Arginine: clinical potential of a semi-essential amino acid. Altern Med Rev 7:512–522
Asakura Y, Kimura E, Usuda Y, Kawahara Y, Matsui K, Osumi T, Nakamatsu T (2007) Altered metabolic flux due to deletion of odhA causes L-glutamate overproduction in Corynebacterium glutamicum. Appl Environ Microbiol 73:1308–1319
Atsumi S, Hanai T, Liao JC (2008) Non-fermentative pathways for synthesis of branched-chain higher alcohols as biofuels. Nature 451:86–89
Azuma T, Nakanishi T (1988) Factors affecting L-arginine production in the continuous culture of an l-arginine producer of Corynebacterium acetoacidophilum. J Ferment Technol 3:285–290
Azuma T, Nakanishi T, Sugimoto M (1988) Isolation and characterization of a stable L-arginine producer from continuous culture broth of Corynebacterium acetoacidophilum. J Ferment Technol 3:279–284
Barrett E, Stanton C, Zelder O, Fitzgerald G, Ross RP (2004) Heterologous expression of lactose- and galactose-utilizing pathways from lactic acid bacteria in Corynebacterium glutamicum for production of lysine in whey. Appl Environ Microbiol 70:2861–2866
Bartek T, Makus P, Klein B, Lang S, Oldiges M (2008) Influence of L-isoleucine and pantothenate auxotrophy for L-valine formation in Corynebacterium glutamicum revisited by metabolome analyses. Bioprocess Biosyst Eng 31:217–225
Bartek T, Blombach B, Zönnchen E, Makus P, Lang S, Eikmanns BJ, Oldiges M (2010a) Importance of NADPH supply for improved L-valine formation in Corynebacterium glutamicum. Biotechnol Prog 26:361–371
Bartek T, Zönnchen E, Klein B, Gerstmeir R, Makus P, Lang S, Oldiges M (2010b) Analysing overexpression of L-valine biosynthesis genes in pyruvate-dehydrogenase-deficient Corynebacterium glutamicum. J Ind Microbiol Biotechnol 37:263–270
Becker J, Klopprogge C, Zelder O, Heinzle E, Wittmann C (2005) Amplified expression of fructose 1,6-bisphosphatase in Corynebacterium glutamicum increases in vivo flux through the pentose phosphate pathway and lysine production on different carbon sources. Appl Environ Microbiol 71:8587–8596
Becker J, Klopprogge C, Herold A, Zelder O, Bolten CJ, Wittmann C (2007) Metabolic flux engineering of L-lysine production in Corynebacterium glutamicum—over expression and modification of G6P dehydrogenase. J Biotechnol 132:99–109
Becker J, Klopprogge C, Schröder H, Wittmann C (2009) Metabolic engineering of the tricarboxylic acid cycle for improved lysine production by Corynebacterium glutamicum. Appl Environ Microbiol 75:7866–7869
Becker J, Zelder O, Häfner S, Schröder H, Wittmann C (2011) From zero to hero: design-based systems metabolic engineering of Corynebacterium glutamicum for L-lysine production. Metab Eng 13:159–168
Beckers G, Strösser J, Hildebrandt U, Kalinowski J, Farwick M, Krämer R, Burkovski A (2005) Regulation of AmtR-controlled gene expression in Corynebacterium glutamicum: mechanism and characterization of the AmtR regulon. Mol Microbiol 58:580–595
Blombach B, Schreiner ME, Holátko J, Bartek T, Oldiges M, Eikmanns BJ (2007a) L-valine production with pyruvate dehydrogenase complex-deficient Corynebacterium glutamicum. Appl Environ Microbiol 73:2079–2084
Blombach B, Schreiner ME, Moch M, Oldiges M, Eikmanns BJ (2007b) Effect of pyruvate dehydrogenase complex deficiency on L-lysine production with Corynebacterium glutamicum. Appl Microbiol Biotechnol 76:615–623
Blombach B, Schreiner ME, Bartek T, Oldiges M, Eikmanns BJ (2008) Corynebacterium glutamicum tailored for high-yield L-valine production. Appl Microbiol Biotechnol 79:471–479
Blombach B, Arndt A, Auchter M, Eikmanns BJ (2009) L-valine production during growth of pyruvate dehydrogenase complex-deficient Corynebacterium glutamicum in the presence of ethanol or by inactivation of the transcriptional regulator SugR. Appl Environ Microbiol 75:1197–1200
Bolten CJ, Schröder H, Dickschat J, Wittmann C (2010) Towards methionine overproduction in Corynebacterium glutamicum: methanethiol and dimethyldisulfide as reduced sulfur sources. J Microbiol Biotechnol 20:1196–1203
Bott M, Niebisch A (2003) The respiratory chain of Corynebacterium glutamicum. J Biotechnol 104:129–153
Brockmann-Gretza O, Kalinowski J (2006) Global gene expression during stringent response in Corynebacterium glutamicum in presence and absence of the rel gene encoding (p)ppGpp synthase. BMC Genomics 7:230
Brune I, Jochmann N, Brinkrolf K, Hüser AT, Gerstmeir R, Eikmanns BJ, Kalinowski J, Pühler A, Tauch A (2007) The IclR-type transcriptional repressor LtbR regulates the expression of leucine and tryptophan biosynthesis genes in the amino acid producer Corynebacterium glutamicum. J Bacteriol 189:2720–2733
Buckland BC, Lilly MD (1993) Fermentation: an overview. In: Stephanopoulos G (ed) Biotechnology, vol 3, 2nd edn, Bioprocessing. VCH Verlagsgesellschaft mbH, Weinheim, pp 7–22
Burkovski A (2008) Corynebacteria: genomics and molecular biology. Caister Academic, Norfolk
Burkovski A, Krämer R (2002) Bacterial amino acid transport proteins: occurrence, functions, and significance for biotechnological applications. Appl Microbiol Biotechnol 58:265–274
Chinen A, Kozlov YI, Hara Y, Izui H, Yasueda H (2007) Innovative metabolic pathway design for efficient L-glutamate production by suppressing CO2 emission. J Biosci Bioeng 103:262–269
Cramer A, Gerstmeir R, Schaffer S, Bott M, Eikmanns BJ (2006) Identification of RamA, a novel LuxR-type regulator of genes involved in acetate metabolism of Corynebacterium glutamicum. J Bacteriol 188:2554–2567
Curis E, Crenn P, Cynober L (2007) Citrulline and the gut. Curr Opin Clin Nutr Metab Care 10:620–626
Dassler T, Maier T, Winterhalter C, Böck A (2000) Identification of a major facilitator protein from Escherichia coli involved in efflux of metabolites of the cysteine pathway. Mol Microbiol 36:1101–1112
Diesveld R, Tietze N, Fürst O, Reth A, Bathe B, Sahm H, Eggeling L (2008) Activity of exporters of Escherichia coli in Corynebacterium glutamicum, and their use to increase L-threonine production. J Mol Microbiol Biotechnol 16:198–207
Dong X, Quinn PJ, Wang X (2011) Metabolic engineering of Escherichia coli and Corynebacterium glutamicum for the production of L-threonine. Biotechnol Adv 29:11–23
Ebbighausen H, Weil B, Krämer R (1989) Transport of branched-chain amino acids in Corynebacterium glutamicum. Arch Microbiol 151:238–244
Eggeling L, Bott M (2005) Handbook of Corynebacterium glutamicum. CRC, Boca Raton, FL
Eggeling L, Oberle S, Sahm H (1998) Improved L-lysine yield with Corynebacterium glutamicum: use of dapA resulting in increased flux combined with growth limitation. Appl Microbiol Biotechnol 49:24–30
Einsele A (1978) Scaling-up bioreactors. Proc Biochem 7:1–14
Elisáková V, Pátek M, Holátko J, Nesvera J, Leyval D, Goergen JL, Delaunay S (2005) Feedback-resistant acetohydroxy acid synthase increases valine production in Corynebacterium glutamicum. Appl Environ Microbiol 71:207–213
Engels V, Lindner SN, Wendisch VF (2008) The global repressor SugR controls expression of genes of glycolysis and of the L-lactate dehydrogenase LdhA in Corynebacterium glutamicum. J Bacteriol 190:8033–8044
Figge R, Soucaille P, Barbier G, Bestel-Corre G, Boisart C, Chateau M (2009) Increasing methionine yield. International Patent Application WO 2009/043803 A2
Flores N, Xiao J, Berry A, Bolivar F, Valle F (1996) Pathway engineering for the production of aromatic compounds in Escherichia coli. Nat Biotechnol 14:620–623
Follmann M, Becker M, Ochrombel I, Ott V, Krämer R, Marin K (2009a) Potassium transport in Corynebacterium glutamicum is facilitated by the putative channel protein CglK, which is essential for pH homeostasis and growth at acidic pH. J Bacteriol 191:2944–2952
Follmann M, Ochrombel I, Krämer R, Trötschel C, Poetsch A, Rückert C, Hüser A, Persicke M, Seiferling D, Kalinowski J, Marin K (2009b) Functional genomics of pH homeostasis in Corynebacterium glutamicum revealed novel links between pH response, oxidative stress, iron homeostasis and methionine synthesis. BMC Genomics 10:621
Franke I, Resch A, Dassler T, Maier T, Böck A (2003) YfiK from Escherichia coli promotes export of O-acetylserine and cysteine. J Bacteriol 185:1161–1166
Fudou R, Jojima Y, Seto A, Yamada K, Kimura E, Nakamatsu T, Hiraishi A, Yamanaka S (2002) Corynebacterium efficiens sp. nov., a glutamic-acid-producing species from soil and vegetables. Int J Syst Evol Microbiol 52:1127–1131
Gerstmeir R, Cramer A, Dangel P, Schaffer S, Eikmanns BJ (2004) RamB, a novel transcriptional regulator of genes involved in acetate metabolism of Corynebacterium glutamicum. J Bacteriol 186:2798–2809
Glansdorff N, Xu Y (2007) Microbial arginine biosynthesis: pathway, regulation and industrial production. In: Wendisch VF (ed) Microbiology monographs, amino acid biosynthesis – pathways, regulation and metabolic engineering. Springer, Berlin, pp 219–257
Gunji Y, Yasueda H (2006) Enhancement of L-lysine production in methylotroph Methylophilus methylotrophus by introducing a mutant LysE exporter. J Biotechnol 127:1–13
Gutmann M, Hoischen C, Krämer R (1992) Carrier-mediated glutamate secretion by Corynebacterium glutamicum under biotin limitation. Biochim Biophys Acta 1112:115–123
Haitani Y, Awano N, Yamazaki M, Wada M, Nakamori S, Takagi H (2006) Functional analysis of L-serine O-acetyltransferase from Corynebacterium glutamicum. FEMS Microbiol Lett 255:156–163
Hänβler E, Müller T, Jessberger N, Völzke A, Plassmeier J, Kalinowski J, Krämer R, Burkovski A (2007) FarR, a putative regulator of amino acid metabolism in Corynebacterium glutamicum. Appl Microbiol Biotechnol 76:625–632
Hashimoto S, Katsumata R (1993) Overproduction of alanine by Arthrobacter strains with glucose-nonrepressible L-alanine dehydrogenase. Biotechnol Lett 15:1117–1122
Hashimoto S, Katsumata R (1998) L-Alanine fermentation by an alanine racemase deficient mutant of the DL-alanine hyperproducing bacterium, Arthrobacter oxydans HAP-1. J Ferment Bioeng 86:346–351
Hashimoto S, Katsumata R (1999) Mechanism of alanine hyperproduction by arthrobacter oxydans HAP-1: metabolic shift to fermentation under nongrowth aerobic conditions. Appl Environ Microbiol 65:2781–2783
Hayashi M, Mizoguchi H, Ohnishi J, Mitsuhashi S, Yonetani Y, Hashimoto S, Ikeda M (2006a) A leuC mutation leading to increased L-lysine production and rel-independent global expression changes in Corynebacterium glutamicum. Appl Microbiol Biotechnol 72:783–789
Hayashi M, Ohnishi J, Mitsuhashi S, Yonetani Y, Hashimoto S, Ikeda M (2006b) Transcriptome analysis reveals global expression changes in an industrial L-lysine producer of Corynebacterium glutamicum. Biosci Biotechnol Biochem 70:546–550
Haynes JA, Britz ML (1990) The effect of growth conditions of Corynebacterium glutamicum on the transformation frequency obtained by electroporation. J Gen Microbiol 136:255–263
Hermann T (2003) Industrial production of amino acids by coryneform bacteria. J Biotechnol 104:155–172
Hirao T, Nakano T, Azuma T, Sugimoto M, Nakanishi T (1989) L-lysine production in continuous culture of an L-lysine hyper- producing mutant of Corynebacterium glutamicum. Appl Microbiol Biotechnol 32:269–273
Holátko J, Elisáková V, Prouza M, Sobotka M, Nesvera J, Pátek M (2009) Metabolic engineering of the L-valine biosynthesis pathway in Corynebacterium glutamicum using promoter activity modulation. J Biotechnol 139:203–210
Hols P, Kleerebezem M, Schanck AN, Ferain T, Hugenholtz J, Delcour J, de Vos WM (1999) Conversion of Lactococcus lactis from homolactic to homoalanine fermentation through metabolic engineering. Nat Biotechnol 17:588–592
Hwang BJ, Park SD, Kim Y, Kim P, Lee HS (2007) Biochemical analysis on the parallel pathways of methionine biosynthesis in Corynebacterium glutamicum. J Microbiol Biotechnol 17:1010–1017
Ikeda M (2003) Amino acid production processes. In: Faurie R, Thommel J (eds) Adv Biochem Eng Biotechnol, vol 79, Microbial production of L-amino acids. Springer, Berlin, pp 1–35
Ikeda M, Katsumata R (1992) Metabolic engineering to produce tyrosine or phenylalanine in a tryptophan-producing Corynebacterium glutamicum strain. Appl Environ Microbiol 58:781–785
Ikeda M, Katsumata R (1994) Transport of aromatic amino acids and its influence on overproduction of the amino acids in Corynebacterium glutamicum. J Ferment Bioeng 78:420–425
Ikeda M, Katsumata R (1995) Tryptophan production by transport mutants of Corynebacterium glutamicum. Biosci Biotechnol Biochem 59:1600–1602
Ikeda M, Katsumata R (1998) A novel system with positive selection for the chromosomal integration of replicative plasmid DNA in Corynebacterium glutamicum. Microbiology 144:1863–1868
Ikeda M, Katsumata R (1999) Hyperproduction of tryptophan by Corynebacterium glutamicum with the modified pentose phosphate pathway. Appl Environ Microbiol 65:2497–2502
Ikeda M, Nakagawa S (2003) The Corynebacterium glutamicum genome: features and impacts on biotechnological process. Appl Microbiol Biotechnol 62:99–109
Ikeda M, Nakanishi K, Kino K, Katsumata R (1994) Fermentative production of tryptophan by a stable recombinant strain of Corynebacterium glutamicum with a modified serine-biosynthetic pathway. Biosci Biotechnol Biochem 58:674–678
Ikeda M, Okamoto K, Katsumata R (1999) Cloning of the transketolase gene and the effect of its dosage on aromatic amino acid production in Corynebacterium glutamicum. Appl Microbiol Biotechnol 51:201–206
Ikeda M, Ohnishi J, Mitsuhashi S (2005) Genome breeding of an amino acid-producing Corynebacterium glutamicum mutant. In: Barredo JLS (ed) Microbial processes and products. Humana, Totowa, pp 179–189
Ikeda M, Ohnishi J, Hayashi M, Mitsuhashi S (2006) A genome-based approach to create a minimally mutated Corynebacterium glutamicum strain for efficient L-lysine production. J Ind Microbiol Biotechnol 33:610–615
Ikeda M, Baba M, Tsukamoto N, Komatsu T, Mitsuhashi S, Takeno S (2009a) Elucidation of genes relevant to the microaerobic growth of Corynebacterium glutamicum. Biosci Biotechnol Biochem 73:2806–2808
Ikeda M, Mitsuhashi S, Tanaka K, Hayashi M (2009b) Reengineering of a Corynebacterium glutamicum L-arginine and L-citrulline producer. Appl Environ Microbiol 75:1635–1641
Ikeda M, Takeno S, Mizuno Y, Mitsuhashi S (2010) Process for producing useful substance. International Patent Application WO 2010/024267 A1
Ikeda M, Mizuno Y, Awane S, Hayashi M, Mitsuhashi S, Takeno S (2011) Identification and application of a different glucose uptake system that functions as an alternative to the phosphotransferase system in Corynebacterium glutamicum. Appl Microbiol Biotechnol 90:1443–1451
Ishizaki A, Takasaki S, Furuta Y (1993) Cell recycled fermentation of glutamate using a novel cross-flow filtration system with constant air supply. J Ferment Bioeng 76:316–320
Jojima T, Fujii M, Mori E, Inui M, Yukawa H (2010) Engineering of sugar metabolism of Corynebacterium glutamicum for production of amino acid L-alanine under oxygen deprivation. Appl Microbiol Biotechnol 87:159–165
Kabus A, Georgi T, Wendisch VF, Bott M (2007a) Expression of the Escherichia coli pntAB genes encoding a membrane-bound transhydrogenase in Corynebacterium glutamicum improves L-lysine formation. Appl Microbiol Biotechnol 75:47–53
Kabus A, Niebisch A, Bott M (2007b) Role of cytochrome bd oxidase from Corynebacterium glutamicum in growth and lysine production. Appl Environ Microbiol 73:861–868
Kalinowski J, Bathe B, Bartels D, Bischoff N, Bott M, Burkovski A, Dusch N, Eggeling L, Eikmanns BJ, Gaigalat L, Goesmann A, Hartmann M, Huthmacher K, Krämer R, Linke B, McHardy AC, Meyer F, Möckel B, Pfefferle W, Pühler A, Rey DA, Rückert C, Rupp O, Sahm H, Wendisch VF, Wiegräbe I, Tauch A (2003) The complete Corynebacterium glutamicum ATCC 13032 genome sequence and its impact on the production of L-aspartate-derived amino acids and vitamins. J Biotechnol 104:5–25
Kallio PT, Kim DJ, Tsai PS, Bailey JE (1994) Intracellular expression of Vitreoscilla hemoglobin alters Escherichia coli energy metabolism under oxygen-limited conditions. Eur J Biochem 219:201–208
Kaneko H, Sakaguchi K (1979) Fusion of protoplasts and genetic recombination of Brevibacterium flavum. Agric Biol Chem 43:1007–1013
Karasawa M, Tosaka O, Ikeda S, Yoshii H (1986) Application of protoplast fusion to the development of L-threonine and L-lysine producers. Agric Biol Chem 50:339–346
Kase H, Nakayama K (1974) Mechanism of L-threonine and L-lysine production by analog-resistant mutants of Corynebacterium glutamicum. Agric Biol Chem 38:993–1000
Katsumata R, Hashimoto S (1996) Process for producing alanine. US Patent 5 559 016
Katsumata R, Ikeda M (1993) Hyperproduction of tryptophan in Corynebacterium glutamicum by pathway engineering. Biotechnology 11:921–925
Katsumata R, Ozaki A, Oka T, Furuya A (1984) Protoplast transformation of glutamate-producing bacteria with plasmid DNA. J Bacteriol 159:306–311
Katsumata R, Mizukami T, Kikuchi Y, Kino K (1986) Threonine production by the lysine producing strain of Corynebacterium glutamicum with amplified threonine biosynthetic operon. In: Alacevic M, Hranueli D, Toman Z (eds) Genetics of industrial microorganisms. Pliva Publishing Co., Yugoslavia, pp 217–226
Kawaguchi H, Vertès AA, Okino S, Inui M, Yukawa H (2006) Engineering of a xylose metabolic pathway in Corynebacterium glutamicum. Appl Environ Microbiol 72:3418–3428
Kawaguchi H, Sasaki M, Vertès AA, Inui M, Yukawa H (2008) Engineering of an L-arabinose metabolic pathway in Corynebacterium glutamicum. Appl Microbiol Biotechnol 77:1053–1062
Kawahara Y, Takahashi-Fuke K, Shimizu E, Nakamatsu T, Nakamori S (1997) Relationship between the glutamate production and the activity of 2-oxoglutarate dehydrogenase in Brevibacterium lactofermentum. Biosci Biotechnol Biochem 61:1109–1112
Kennerknecht N, Sahm H, Yen MR, Patek M, Saier MH Jr, Eggeling L (2002) Export of L-isoleucine from Corynebacterium glutamicum: a two-gene-encoded member of a new translocator family. J Bacteriol 184:3947–3956
Kiefer P, Heinzle E, Zelder O, Wittmann C (2004) Comparative metabolic flux analysis of lysine-producing Corynebacterium glutamicum cultured on glucose or fructose. Appl Environ Microbiol 70:229–239
Kim HJ, Kim TH, Kim Y, Lee HS (2004) Identification and characterization of glxR, a gene involved in regulation of glyoxylate bypass in Corynebacterium glutamicum. J Bacteriol 186:3453–3460
Kim TH, Kim HJ, Park JS, Kim Y, Kim P, Lee HS (2005a) Functional analysis of sigH expression in Corynebacterium glutamicum. Biochem Biophys Res Commun 331:1542–1547
Kim TH, Park JS, Kim HJ, Kim Y, Kim P, Lee HS (2005b) The whcE gene of Corynebacterium glutamicum is important for survival following heat and oxidative stress. Biochem Biophys Res Commun 337:757–764
Kim J, Fukuda H, Hirasawa T, Nagahisa K, Nagai K, Wachi M, Shimizu H (2009a) Requirement of de novo synthesis of the OdhI protein in penicillin-induced glutamate production by Corynebacterium glutamicum. Appl Microbiol Biotechnol. doi:10.1007/s00253-009-2360-6
Kim J, Hirasawa T, Sato Y, Nagahisa K, Furusawa C, Shimizu H (2009b) Effect of odhA overexpression and odhA antisense RNA expression on Tween-40-triggered glutamate production by Corynebacterium glutamicum. Appl Microbiol Biotechnol 81:1097–1106
Kimura E (2003) Metabolic engineering of glutamate production. In: Faurie R, Thommel J (eds) Adv Biochem Eng Biotechnol, vol 79, Microbial production of L-amino acids. Springer, Berlin, pp 37–58
Kimura E (2005) L-Glutamate production. In: Eggeling L, Bott M (eds) Handbook of Corynebacterium glutamicum. CRC, Boca Raton, FL, pp 439–463
Kimura E, Yagoshi C, Kawahara Y, Ohsumi T, Nakamatsu T, Tokuda H (1999) Glutamate overproduction in Corynebacterium glutamicum triggered by a decrease in the level of a complex comprising DtsR and a biotin-containing subunit. Biosci Biotechnol Biochem 63:1274–1278
Kinoshita S, Nakayama K (1978) Amino acids. In: Rose AH (ed) Primary products of metabolism. Academic, London, pp 209–261
Kinoshita S, Udaka S, Shimono M (1957) Studies on the amino acid fermentation, part I. Production of L-glutamic acid by various microorganisms. J Gen Appl Microbiol 3:193–205
Kitai A (1972) Alanine. In: Yamada K, Kinoshita S, Tsunoda T, Aida K (eds) The microbial production of amino acids. John Wiley and Sons, New York, NY, pp 325–337
Kjeldsen KR, Nielsen J (2009) In silico genome-scale reconstruction and validation of the Corynebacterium glutamicum metabolic network. Biotechnol Bioeng 102:583–597
Koch DJ, Rückert C, Albersmeier A, Hüser AT, Tauch A, Pühler A, Kalinowski J (2005) The transcriptional regulator SsuR activates expression of the Corynebacterium glutamicum sulphonate utilization genes in the absence of sulphate. Mol Microbiol 58:480–494
Krings E, Krumbach K, Bathe B, Kelle R, Wendisch VF, Sahm H, Eggeling L (2006) Characterization of myo-inositol utilization by Corynebacterium glutamicum: the stimulon, identification of transporters, and influence on L-lysine formation. J Bacteriol 188:8054–8061
Krömer JO, Sorgenfrei O, Klopprogge K, Heinzle E, Wittmann C (2004) In-depth profiling of lysine-producing Corynebacterium glutamicum by combined analysis of the transcriptome, metabolome, and fluxome. J Bacteriol 186:1769–1784
Krömer JO, Wittmann C, Schröder H, Heinzle E (2006) Metabolic pathway analysis for rational design of L-methionine production by Eschrichia coli and Corynebacterium glutamicum. Metab Eng 8:353–369
Krömer JO, Bolten CJ, Heinzle E, Schröder H, Wittmann C (2008) Physiological response of Corynebacterium glutamicum to oxidative stress induced by deletion of the transcriptional repressor McbR. Microbiology 154:3917–3930
Lange C, Rittmann D, Wendisch VF, Bott M, Sahm H (2003) Global expression profiling and physiological characterization of Corynebacterium glutamicum grown in the presence of L-valine. Appl Environ Microbiol 69:2521–2532
Lee HS, Hwang BJ (2003) Methionine biosynthesis and its regulation in Corynebacterium glutamicum: parallel pathways of transsulfuration and direct sulfhydrylation. Appl Microbiol Biotechnol 62:459–467
Lee SY, Shin HS, Park JS, Kim YH, Min J (2010) Proline reduces the binding of transcriptional regulator ArgR to upstream of argB in Corynebacterium glutamicum. Appl Microbiol Biotechnol 86:235–242
Leuchtenberger W (1996) Amino acids – technical production and use. In: Roehr M (ed) Biotechnology, vol 6, 2nd edn, Products of primary metabolism. VCH Verlagsgesellschaft mbH, Weinheim, pp 465–502
Leuchtenberger W, Huthmacher K, Drauz K (2005) Biotechnological production of amino acids and derivatives: current status and prospects. Appl Microbiol Biotechnol 69:1–8
Li L, Wada M, Yokota A (2007) A comparative proteomic approach to understand the adaptations of an H+-ATPase-defective mutant of Corynebacterium glutamicum ATCC14067 to energy deficiencies. Proteomics 7:3348–3357
Liu Q, Zhang J, Wei XX, Ouyang SP, Wu Q, Chen GQ (2008) Microbial production of L-glutamate and L-glutamine by recombinant Corynebacterium glutamicum harboring Vitreoscilla hemoglobin gene vgb. Appl Microbiol Biotechnol 77:1297–1304
Mampel J, Schröder H, Haefner S, Sauer U (2005) Single-gene knockout of a novel regulatory element confers ethionine resistance and elevates methionine production in Corynebacterium glutamicum. Appl Microbiol Biotechnol 68:228–236
Marienhagen J, Eggeling L (2008) Metabolic function of Corynebacterium glutamicum aminotransferases AlaT and AvtA and impact on L-valine production. Appl Environ Microbiol 74:7457–7462
Marx A, Hans S, Mockel B, Bathe B, de Graaf AA (2003) Metabolic phenotype of phosphoglucose isomerase mutants of Corynebacterium glutamicum. J Biotechnol 104:185–197
McWilliams A (2010) Biotechnologies for medical applications: global markets. Report code: BIO072A, BCC Research (http://www.bccresearch.com)
Mitsuhashi S, Hayashi M, Ohnishi J, Ikeda M (2006) Disruption of malate: quinone oxidoreductase increases L-lysine production by Corynebacterium glutamicum. Biosci Biotechnol Biochem 70:2803–2806
Miwa K, Matsui K, Terabe M, Ito K, Ishida M, Takagi H, Nakamori S, Sano K (1985) Construction of novel shuttle vector and a cosmid vector for the glutamic acid-producing bacteria Brevibacterium lactofermentum and Corynebacterium glutamicum. Gene 39:281–286
Möckel B, Pfefferle W, Huthmacher K, Rückert C, Kalinowski J, Pühler A, Binder M, Greissinger D, Thierbach G (2002) Nucleotide sequences which code for the metY gene. International Patent Application WO 02/18613
Möker N, Krämer J, Unden G, Krämer R, Morbach S (2007) In vitro analysis of the two-component system MtrB-MtrA from Corynebacterium glutamicum. J Bacteriol 189:3645–3649
Moon MW, Kim HJ, Oh TK, Shin CS, Lee JS, Kim SJ, Lee JK (2005) Analyses of enzyme II gene mutants for sugar transport and heterologous expression of fructokinase gene in Corynebacterium glutamicum ATCC 13032. FEMS Microbiol Lett 244:259–266
Morbach S, Sahm H, Eggeling L (1996) L-Isoleucine production with Corynebacterium glutamicum: further flux increase and limitation of export. Appl Environ Microbiol 62:4345–4351
Nakamura J, Hirano S, Ito H, Wachi M (2007) Mutations of the Corynebacterium glutamicum NCgl1221 gene, encoding a mechanosensitive channel homolog, induce L-glutamic acid production. Appl Environ Microbiol 73:4491–4498
Nakayama K, Kitada S, Kinoshita S (1961) Studies on lysine fermentation. I. The control mechanism on lysine accumulation by homoserine and threonine. J Gen Appl Microbiol 7:145–154
Niebisch A, Kabus A, Schultz C, Weil B, Bott M (2006) Corynebacterial protein kinase G controls 2-oxoglutarate dehydrogenase activity via the phosphorylation status of the OdhI protein. J Biol Chem 281:12300–12307
Nishimura T, Vertès AA, Shinoda Y, Inui M, Yukawa H (2007) Anaerobic growth of Corynebacterium glutamicum using nitrate as a terminal electron acceptor. Appl Microbiol Biotechnol 75:889–897
Nishio Y, Nakamura Y, Kawarabayasi Y, Usuda Y, Kimura E, Sugimoto S, Matsui K, Yamagishi A, Kikuchi H, Ikeo K, Gojobori T (2003) Comparative complete genome sequence analysis of the amino acid replacements responsible for the thermostability of Corynebacterium efficiens. Genome Res 13:1572–1579
Nottebrock D, Meyer U, Krämer R, Morbach S (2003) Molecular and biochemical characterization of mechanosensitive channels in Corynebacterium glutamicum. FEMS Microbiol Lett 218:305–309
Ohnishi J, Ikeda M (2006) Comparisons of potentials for L-lysine production among different Corynebacterium glutamicum strains. Biosci Biotechnol Biochem 70:1017–1020
Ohnishi J, Mitsuhashi S, Hayashi M, Ando S, Yokoi H, Ochiai K, Ikeda M (2002) A novel methodology employing Corynebacterium glutamicum genome information to generate a new L-lysine-producing mutant. Appl Microbiol Biotechnol 58:217–223
Ohnishi J, Hayashi M, Mitsuhashi S, Ikeda M (2003) Efficient 40°C fermentation of L-lysine by a new Corynebacterium glutamicum mutant developed by genome breeding. Appl Microbiol Biotechnol 62:69–75
Ohnishi J, Katahira R, Mitsuhashi S, Kakita S, Ikeda M (2005) A novel gnd mutation leading to increased L-lysine production in Corynebacterium glutamicum. FEMS Microbiol Lett 242:265–274
Ozaki A, Katsumata R, Oka T, Furuya A (1985) Cloning of the genes concerned in phenylalanine biosynthesis in Corynebacterium glutamicum and its application to breeding of a phenylalanine producing strain. Agric Biol Chem 49:2925–2930
Park JH, Lee SY (2010) Fermentative production of branched chain amino acids: a focus on metabolic engineering. Appl Microbiol Biotechnol 85:491–506
Park SD, Lee JY, Sim SY, Kim Y, Lee HS (2007) Characteristics of methionine production by an engineered Corynebacterium glutamicum strain. Metab Eng 9:327–336
Pátek M (2007) Branched-chain amino acids. In: Wendisch VF (ed) Microbiology monographs, amino acid biosynthesis – pathways, regulation and metabolic engineering. Springer, Berlin, pp 129–162
Peter H, Burkovski A, Krämer R (1996) Isolation, characterization, and expression of the Corynebacterium glutamicum betP gene, encoding the transport system for the compatible solute glycine betaine. J Bacteriol 178:5229–5234
Peter H, Weil B, Burkovski A, Krämer R, Morbach S (1998) Corynebacterium glutamicum is equipped with four secondary carriers for compatible solutes: identification, sequencing, and characterization of the proline/ectoine uptake system, ProP, and the ectoine/proline/glycine betaine carrier, EctP. J Bacteriol 180:6005–6012
Petersen S, Mack C, de Graaf AA, Riedel C, Eikmanns BJ, Sahm H (2001) Metabolic consequences of altered phosphoenolpyruvate carboxykinase activity in Corynebacterium glutamicum reveal anaplerotic mechanisms in vivo. Metab Eng 3:344–361
Peters-Wendisch PG, Schiel B, Wendisch VF, Katsoulidis E, Möckel B, Sahm H, Eikmanns BJ (2001) Pyruvate carboxylase is a major bottleneck for glutamate and lysine production by Corynebacterium glutamicum. J Mol Microbiol Biotechnol 3:295–300
Peters-Wendisch P, Stolz M, Etterich H, Kennerknecht N, Sahm H, Eggeling L (2005) Metabolic engineering of Corynebacterium glutamicum for L-serine production. Appl Environ Microbiol 71:7139–7144
Pfefferle W, Möckel B, Bathe B, Marx A (2003) Biotechnological manufacture of lysine. In: Faurie R, Thommel J (eds) Adv Biochem Eng Biotechnol, vol 79, Microbial production of L-amino acids. Springer, Berlin, pp 59–112
Radmacher E, Vaitsikova A, Burger U, Krumbach K, Sahm H, Eggeling L (2002) Linking central metabolism with increased pathway flux: L-valine accumulation by Corynebacterium glutamicum. Appl Environ Microbiol 68:2246–2250
Rey DA, Pühler A, Kalinowski J (2003) The putative transcriptional repressor McbR, member of the TetR-family, is involved in the regulation of the metabolic network directing the synthesis of sulfur containing amino acids in Corynebacterium glutamicum. J Biotechnol 103:51–65
Rey DA, Nentwich SS, Koch DJ, Rückert C, Pühler A, Tauch A, Kalinowski J (2005) The McbR repressor modulated by the effector substance S-adenosylhomocysteine controls directly the transcription of a regulon involved in sulphur metabolism of Corynebacterium glutamicum ATCC 13032. Mol Microbiol 56:871–887
Riedel C, Rittmann D, Dangel P, Möckel B, Sahm H, Eikmanns BJ (2001) Characterization, expression, and inactivation of the phosphoenolpyruvate carboxykinase gene from Corynebacterium glutamicum and significance of the enzyme for growth and amino acid production. J Mol Microbiol Biotechnol 3:573–583
Rieping M, Hermann T (2007) L-Threonine. In: Wendisch VF (ed) Microbiology monographs, amino acid biosynthesis – pathways, regulation and metabolic engineering. Springer, Berlin, pp 71–92
Rittmann D, Lindner SN, Wendisch VF (2008) Engineering of a glycerol utilization pathway for amino acid production by Corynebacterium glutamicum. Appl Environ Microbiol 74:6216–6222
Sano K, Shiio I (1971) Microbial production of L-lysine. IV. Selection of lysine-producing mutants from Brevibacterium flavum by detecting threonine sensitivity or halo-forming method. J Gen Appl Microbiol 17:97–113
Sano K, Yokozeki K, Tamura F, Yasuda N, Noda I, Mitsugi K (1977) Microbial conversion of DL-2-amino-Δ2thiazoline-4-carboxylic acid to L-cysteine and L-cystine: screening of microorganisms and identification of products. Appl Environ Microbiol 34:806–810
Santamaria R, Gil JA, Mesas JM, Martin JF (1984) Characterization of an endogenous plasmid and development of cloning vectors and a transformation system in Brevibacterium lactofermentum. J Gen Microbiol 130:2237–2246
Sato H, Orishimo K, Shirai T, Hirasawa T, Nagahisa K, Shimizu H, Wachi M (2008) Distinct roles of two anaplerotic pathways in glutamate production induced by biotin limitation in Corynebacterium glutamicum. J Biosci Bioeng 106:51–58
Sawada K, Zen-In S, Wada M, Yokota A (2010) Metabolic changes in a pyruvate kinase gene deletion mutant of Corynebacterium glutamicum ATCC 13032. Metab Eng 12:401–407
Schaaf S, Bott M (2007) Target genes and DNA-binding sites of the response regulator PhoR from Corynebacterium glutamicum. J Bacteriol 189:5002–5011
Schäfer A, Kalinowski J, Simon R, Seep-Feldhaus A-H, Pühler A (1990) High-frequency conjugal plasmid transfer from gram-negative Escherichia coli to various gram-positive coryneform bacteria. J Bacteriol 172:1663–1666
Schultz C, Niebisch A, Gebel L, Bott M (2007) Glutamate production by Corynebacterium glutamicum: dependence on the oxoglutarate dehydrogenase inhibitor protein OdhI and protein kinase PknG. Appl Microbiol Biotechnol 76:691–700
Schwarzer A, Pühler A (1991) Manipulation of Corynebacterium glutamicum by gene disruption and replacement. Biotechnology 9:84–87
Seibold G, Auchter M, Berens S, Kalinowski J, Eikmanns BJ (2006) Utilization of soluble starch by a recombinant Corynebacterium glutamicum strain: growth and lysine production. J Biotechnol 124:381–391
Shibatani T, Kakimoto T, Chibata I (1979) Stimulation of L-asparate β-decarboxylase formation by L-glutamate in Pseudomonas dacunhae and improved production of L-alanine. Appl Environ Microbiol 38:359–364
Shiio I, Miyajima R (1969) Concerted inhibition and its reversal by end products of aspartate kinase in Brevibacterium flavum. J Biochem 65:849–859
Shiio I, Toride Y, Sugimoto S (1984) Production of lysine by pyruvate dehydrogenase mutants of Brevibacterium flavum. Agric Biol Chem 48:3091–3098
Shimomura Y, Yamamoto Y, Bajotto G, Sato J, Murakami T, Shimomura N, Kobayashi H, Mawatari K (2006) Nutraceutical effects of branched-chain amino acids on skeletal muscle. J Nutr 136:529S–532S
Shingu H, Terui G (1971) Studies on process of glutamic acid fermentation at the enzyme level. Part I. On the change of α-ketoglutaric acid dehydrogenase in the course of culture. J Ferment Technol 49:400–405
Simic P, Sahm H, Eggeling L (2001) L-Threonine export: use of peptides to identify a new translocator from Corynebacterium glutamicum. J Bacteriol 183:5317–5324
Simic P, Willuhn J, Sahm H, Eggeling L (2002) Identification of glyA (encoding serine hydroxymethyltransferase) and its use together with the exporter ThrE to increase L-threonine accumulation by Corynebacterium glutamicum. Appl Environ Microbiol 68:3321–3327
Sindelar G, Wendisch VF (2007) Improving lysine production by Corynebacterium glutamicum through DNA microarray-based identification of novel target genes. Appl Microbiol Biotechnol 76:677–689
Smith GM, Lee SA, Reilly KC, Eiteman MA, Altman E (2006) Fedbatch two-phase production of alanine by a metabolically engineered Escherichia coli. Biotechnol Lett 28:1695–1700
Sprenger GA (2007) Aromatic amino acids. In: Wendisch VF (ed) Microbiology monographs, amino acid biosynthesis – pathways, regulation and metabolic engineering. Springer, Berlin, pp 93–127
Steger R, Weinand M, Krämer R, Morbach S (2004) LcoP, an osmoregulated betaine/ectoine uptake system from Corynebacterium glutamicum. FEBS Lett 573:155–160
Stolz M, Peters-Wendisch P, Etterich H, Gerharz T, Faurie R, Sahm H, Fersterra H, Eggeling L (2007) Reduced folate supply as a key to enhanced L-serine production by Corynebacterium glutamicum. Appl Environ Microbiol 73:750–755
Strelkov S, von Elstermann M, Schomburg D (2004) Comprehensive analysis of metabolites in Corynebacterium glutamicum by gas chromatography/mass spectrometry. Biol Chem 385:853–861
Takeno S, Ohnishi J, Komatsu T, Masaki T, Sen K, Ikeda M (2007) Anaerobic growth and potential for amino acid production by nitrate respiration in Corynebacterium glutamicum. Appl Microbiol Biotechnol 75:1173–1182
Takeno S, Nakamura M, Fukai R, Ohnishi J, Ikeda M (2008) The Cgl1281-encoding putative transporter of the cation diffusion facilitator family is responsible for alkali-tolerance in Corynebacterium glutamicum. Arch Microbiol 190:531–538
Takeno S, Murata R, Kobayashi R, Mitsuhashi S, Ikeda M (2010) Engineering of Corynebacterium glutamicum with an NADPH-generating glycolytic pathway for L-lysine production. Appl Environ Microbiol 76:7154–7160
Tateno T, Fukuda H, Kondo A (2007) Production of L-lysine from starch by Corynebacterium glutamicum displaying α-amylase on its cell surface. Appl Microbiol Biotechnol 74:1213–1220
Trötschel C, Deutenberg D, Bathe B, Burkovski A, Krämer R (2005) Characterization of methionine export in Corynebacterium glutamicum. J Bacteriol 187:3786–3794
Udaka S (1960) Screening method for microorganisms accumulating metabolites and its use in the isolation of Micrococcus glutamicus. J Bacteriol 79:754–755
Udaka S (2008) The discovery of Corynebacterium glutamicum and birth of amino acid fermentation industry in Japan. In: Burkovski A (ed) Corynebacteria: genomics and molecular biology. Caister Academic, Norwich, pp 1–6
Uhlenbusch I, Sahm H, Sprenger GA (1991) Expression of an L-alanine dehydrogenase gene in Zymomonas mobilis and excretion of L-alanine. Appl Environ Microbiol 57:1360–1366
Utagawa T (2004) Arginine metabolism: enzymology, nutrition, and clinical significance. J Nutr 134:2854S–2857S
van der Rest ME, Lange C, Molenaar D (1999) A heat shock following electroporation of Corynebacterium glutamicum with xenogeneic plasmid DNA. Appl Microbiol Biotechnol 52:541–545
Vrljić M, Sahm H, Eggeling L (1996) A new type of transporter with a new type of cellular function: L-lysine export from Corynebacterium glutamicum. Mol Microbiol 22:815–826
Wada M, Takagi H (2006) Metabolic pathways and biotechnological production of L-cysteine. Appl Microbiol Biotechnol 73:48–54
Wada M, Awano N, Haisa K, Takagi H, Nakamori S (2002) Purification, characterization and identification of cysteine desulfhydrase of Corynebacterium glutamicum, and its relationship to cysteine production. FEMS Microbiol Lett 217:103–107
Wada M, Hijikata N, Aoki R, Takesue N, Yokota A (2008) Enhanced valine production in Corynebacterium glutamicum with defective H+-ATPase and C-terminal truncated acetohydroxyacid synthase. Biosci Biotechnol Biochem 72:2959–2965
Webster DA (1987) Structure and function of bacterial hemoglobin and related proteins. In: Eichhorn GC, Marzilli LG (eds) Advances in inorganic chemistry. Elsevier, New York, NY, pp 245–265
Wendisch VF (2007) Microbiology monographs, amino acid biosynthesis – pathways, regulation and metabolic engineering. Springer, Berlin
Wendisch VF, Bott M, Kalinowski J, Oldiges M, Wiechert W (2006) Emerging Corynebacterium glutamicum systems biology. J Biotechnol 124:74–92
Wennerhold J, Bott M (2006) The DtxR regulon of Corynebacterium glutamicum. J Bacteriol 188:2907–2918
Willis LB, Lessard PA, Sinskey AJ (2005) Synthesis of L-threonine and branched-chain amino acids. In: Eggeling L, Bott M (eds) Handbook of Corynebacterium glutamicum. CRC, Boca Raton, FL, pp 511–531
Wittmann C, Heinzle E (2002) Genealogy profiling through strain improvement by using metabolic network analysis: metabolic flux genealogy of several generations of lysine-producing Corynebacteria. Appl Environ Microbiol 68:5843–5859
Yao W, Chu C, Deng X, Zhang Y, Liu M, Zheng P, Sun Z (2009) Display of α-amylase on the surface of Corynebacterium glutamicum cells by using NCgl1221 as the anchoring protein, and production of glutamate from starch. Arch Microbiol 191:751–759
Yoshihama M, Higashiro K, Rao EA, Akedo M, Shanabruch WG, Folletie MT, Walker GC, Sinskey AJ (1985) Cloning vector system for Corynebacterium glutamicum. J Bacteriol 162:591–597
Yukawa H, Omumasaba CA, Nonaka H, Kós P, Okai N, Suzuki N, Suda M, Tsuge Y, Watanabe J, Ikeda Y, Vertès AA, Inui M (2007) Comparative analysis of the Corynebacterium glutamicum group and complete genome sequence of strain R. Microbiology 153:1042–1058
Zhang L, Li Y, Wang Z, Xia Y, Chen W, Tang K (2007a) Recent developments and future prospects of Vitreoscilla hemoglobin application in metabolic engineering. Biotechnol Adv 25:123–136
Zhang X, Jantama K, Moore JC, Shanmugam KT, Ingram LO (2007b) Production of L-alanine by metabolically engineered Escherichia coli. Appl Microbiol Biotechnol 77:355–366
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2013 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Ikeda, M., Takeno, S. (2013). Amino Acid Production by Corynebacterium glutamicum . In: Yukawa, H., Inui, M. (eds) Corynebacterium glutamicum. Microbiology Monographs, vol 23. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-29857-8_4
Download citation
DOI: https://doi.org/10.1007/978-3-642-29857-8_4
Published:
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-29856-1
Online ISBN: 978-3-642-29857-8
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)